const pptxgen = require("pptxgenjs");

const pres = new pptxgen();
pres.layout = "LAYOUT_16x9";
pres.title = "Autocoids: Amine, Peptide & Lipid Derived";
pres.author = "Orris Medical";

// ─── COLOUR PALETTE ───────────────────────────────────────────────
// Dark navy dominant, teal accent, amber highlight
const C = {
  navy:      "0D1B2A",  // dominant bg
  navyMid:   "162338",
  navyLight: "1E3354",
  teal:      "00B4D8",
  tealDark:  "0096C7",
  amber:     "FFB703",
  white:     "FFFFFF",
  offWhite:  "E8F1F5",
  gray:      "8FA3B1",
  lightGray: "C9D8E3",
  cardBg:    "162D44",
  green:     "52B788",
  purple:    "9D4EDD",
  red:       "EF233C",
  orange:    "F4A261",
};

// ─── HELPER: section label bar ────────────────────────────────────
function sectionBar(slide, label, color) {
  slide.addShape(pres.shapes.RECTANGLE, {
    x: 0, y: 0, w: 10, h: 0.55,
    fill: { color },
    line: { color, pt: 0 },
  });
  slide.addText(label, {
    x: 0.3, y: 0, w: 9.4, h: 0.55,
    fontSize: 13, bold: true, color: C.navy, valign: "middle", margin: 0,
  });
}

// ─── HELPER: card box ─────────────────────────────────────────────
function card(slide, x, y, w, h, fillColor, lineColor) {
  slide.addShape(pres.shapes.ROUNDED_RECTANGLE, {
    x, y, w, h, rectRadius: 0.08,
    fill: { color: fillColor || C.cardBg },
    line: { color: lineColor || C.teal, pt: 1.2 },
    shadow: { type: "outer", color: "000000", blur: 8, offset: 3, angle: 135, opacity: 0.25 },
  });
}

// ─── HELPER: accent left bar ──────────────────────────────────────
function accentBar(slide, x, y, h, color) {
  slide.addShape(pres.shapes.RECTANGLE, {
    x, y, w: 0.06, h,
    fill: { color },
    line: { color, pt: 0 },
  });
}

// ─────────────────────────────────────────────────────────────────
// SLIDE 1 — TITLE
// ─────────────────────────────────────────────────────────────────
{
  const s = pres.addSlide();
  s.background = { color: C.navy };

  // Top accent strip
  s.addShape(pres.shapes.RECTANGLE, {
    x: 0, y: 0, w: 10, h: 0.08, fill: { color: C.teal }, line: { color: C.teal, pt: 0 },
  });

  // Large decorative circle (background)
  s.addShape(pres.shapes.ELLIPSE, {
    x: 6.2, y: -1.5, w: 5.5, h: 5.5,
    fill: { color: C.navyLight, transparency: 40 },
    line: { color: C.teal, pt: 1.5 },
  });
  s.addShape(pres.shapes.ELLIPSE, {
    x: 7.0, y: -0.8, w: 3.8, h: 3.8,
    fill: { color: C.teal, transparency: 85 },
    line: { color: C.teal, pt: 0 },
  });

  // Main title
  s.addText("AUTOCOIDS", {
    x: 0.6, y: 1.2, w: 7, h: 1.1,
    fontSize: 52, bold: true, color: C.white,
    charSpacing: 8,
  });

  // Subtitle
  s.addText("Amine · Peptide · Lipid Derived", {
    x: 0.6, y: 2.4, w: 7, h: 0.6,
    fontSize: 22, color: C.teal, italic: true,
  });

  // Horizontal divider
  s.addShape(pres.shapes.RECTANGLE, {
    x: 0.6, y: 3.1, w: 5.5, h: 0.04,
    fill: { color: C.amber }, line: { color: C.amber, pt: 0 },
  });

  // Definition box
  card(s, 0.55, 3.3, 6.2, 1.3, C.navyLight, C.amber);
  s.addText([
    { text: "Autocoids ", options: { bold: true, color: C.amber } },
    { text: "are locally acting endogenous substances produced and acting at or near their site of synthesis. Unlike hormones (systemic) or neurotransmitters (synaptic), they have diverse chemical structures and complex physiological and pathological roles.", options: { color: C.offWhite } },
  ], { x: 0.75, y: 3.4, w: 5.8, h: 1.1, fontSize: 11.5, valign: "middle" });

  // Bottom source
  s.addText("Sources: Katzung's Basic & Clinical Pharmacology 16e · Goodman & Gilman's 13e · Ganong's Physiology 26e", {
    x: 0, y: 5.3, w: 10, h: 0.3,
    fontSize: 8, color: C.gray, align: "center",
  });
}

// ─────────────────────────────────────────────────────────────────
// SLIDE 2 — OVERVIEW / CLASSIFICATION MIND-MAP STYLE
// ─────────────────────────────────────────────────────────────────
{
  const s = pres.addSlide();
  s.background = { color: C.navy };

  sectionBar(s, "CLASSIFICATION OF AUTOCOIDS", C.teal);

  s.addText("Three Major Chemical Classes", {
    x: 0.4, y: 0.65, w: 9.2, h: 0.4,
    fontSize: 16, bold: true, color: C.white,
  });

  // Central circle
  s.addShape(pres.shapes.ELLIPSE, {
    x: 3.75, y: 1.9, w: 2.5, h: 1.8,
    fill: { color: C.navyLight },
    line: { color: C.white, pt: 1.5 },
  });
  s.addText("AUTO-\nCOIDS", {
    x: 3.75, y: 2.0, w: 2.5, h: 1.6,
    fontSize: 18, bold: true, color: C.white, align: "center", valign: "middle",
  });

  // ── AMINE BOX ──
  card(s, 0.2, 1.1, 2.9, 2.5, "152032", C.amber);
  s.addShape(pres.shapes.RECTANGLE, { x: 0.2, y: 1.1, w: 2.9, h: 0.38, fill: { color: C.amber }, line: { color: C.amber, pt: 0 } });
  s.addText("AMINE-DERIVED", { x: 0.25, y: 1.1, w: 2.8, h: 0.38, fontSize: 11, bold: true, color: C.navy, valign: "middle", margin: 0 });
  s.addText([
    { text: "• Histamine\n", options: { bullet: false } },
    { text: "• Serotonin (5-HT)\n", options: { bullet: false } },
    { text: "• Dopamine", options: { bullet: false } },
  ], { x: 0.35, y: 1.56, w: 2.7, h: 1.9, fontSize: 12, color: C.offWhite, valign: "top" });

  // ── PEPTIDE BOX ──
  card(s, 3.55, 4.0, 2.9, 1.55, "152032", C.green);
  s.addShape(pres.shapes.RECTANGLE, { x: 3.55, y: 4.0, w: 2.9, h: 0.38, fill: { color: C.green }, line: { color: C.green, pt: 0 } });
  s.addText("PEPTIDE-DERIVED", { x: 3.6, y: 4.0, w: 2.8, h: 0.38, fontSize: 11, bold: true, color: C.navy, valign: "middle", margin: 0 });
  s.addText("• Bradykinin  • ANP/BNP\n• Substance P  • Endothelins\n• Angiotensin II", {
    x: 3.7, y: 4.42, w: 2.7, h: 1.05, fontSize: 10.5, color: C.offWhite, valign: "top",
  });

  // ── LIPID BOX ──
  card(s, 6.9, 1.1, 2.85, 2.5, "152032", C.purple);
  s.addShape(pres.shapes.RECTANGLE, { x: 6.9, y: 1.1, w: 2.85, h: 0.38, fill: { color: C.purple }, line: { color: C.purple, pt: 0 } });
  s.addText("LIPID-DERIVED", { x: 6.95, y: 1.1, w: 2.75, h: 0.38, fontSize: 11, bold: true, color: C.white, valign: "middle", margin: 0 });
  s.addText([
    { text: "Prostanoids (PGs, TxA2, PGI2)\n", options: {} },
    { text: "Leukotrienes (LTB4, LTC4/D4/E4)\n", options: {} },
    { text: "Lipoxins (LXA4, LXB4)\n", options: {} },
    { text: "PAF", options: {} },
  ], { x: 7.05, y: 1.56, w: 2.65, h: 1.9, fontSize: 10.5, color: C.offWhite, valign: "top" });

  // Connector lines (approximate)
  s.addShape(pres.shapes.RECTANGLE, { x: 3.1, y: 2.5, w: 0.65, h: 0.06, fill: { color: C.amber }, line: { color: C.amber, pt: 0 } });
  s.addShape(pres.shapes.RECTANGLE, { x: 4.85, y: 4.0, w: 0.06, h: 0.35, fill: { color: C.green }, line: { color: C.green, pt: 0 } });
  s.addShape(pres.shapes.RECTANGLE, { x: 6.25, y: 2.5, w: 0.65, h: 0.06, fill: { color: C.purple }, line: { color: C.purple, pt: 0 } });

  // Key note
  s.addText("All act locally with short half-lives and are not stored as classical hormones", {
    x: 0.3, y: 5.22, w: 9.4, h: 0.3,
    fontSize: 9.5, color: C.gray, align: "center", italic: true,
  });
}

// ─────────────────────────────────────────────────────────────────
// SLIDE 3 — HISTAMINE
// ─────────────────────────────────────────────────────────────────
{
  const s = pres.addSlide();
  s.background = { color: C.navy };

  sectionBar(s, "AMINE-DERIVED  |  HISTAMINE", C.amber);

  // Synthesis pathway box
  card(s, 0.25, 0.65, 3.6, 1.3, C.navyLight, C.amber);
  s.addText("SYNTHESIS", { x: 0.35, y: 0.68, w: 3.4, h: 0.28, fontSize: 10, bold: true, color: C.amber });
  s.addText("L-Histidine → [Histidine decarboxylase] → Histamine\nStored in: Mast cells, Basophils, Platelets, Gastric ECL cells\nMetab: N-methylhistamine, Imidazoleacetic acid (MAO/DAO)", {
    x: 0.35, y: 0.98, w: 3.4, h: 0.9, fontSize: 9.5, color: C.offWhite,
  });

  // Storage/release box
  card(s, 4.05, 0.65, 5.6, 1.3, C.navyLight, C.orange);
  s.addText("RELEASE TRIGGERS", { x: 4.15, y: 0.68, w: 5.4, h: 0.28, fontSize: 10, bold: true, color: C.orange });
  s.addText("IgE-mediated (Type I hypersensitivity)  •  Tissue injury & trauma\nBasic drugs/contrast media (direct mast cell degranulation)\nNeuropeptides  •  Complement (C3a, C5a)  •  High-histamine foods", {
    x: 4.15, y: 0.98, w: 5.4, h: 0.9, fontSize: 9.5, color: C.offWhite,
  });

  // Receptor table header
  s.addShape(pres.shapes.RECTANGLE, {
    x: 0.25, y: 2.08, w: 9.5, h: 0.34,
    fill: { color: C.amber }, line: { color: C.amber, pt: 0 },
  });
  s.addText("RECEPTOR  |  COUPLING  |  LOCATION  |  KEY EFFECTS", {
    x: 0.3, y: 2.08, w: 9.4, h: 0.34, fontSize: 10, bold: true, color: C.navy, valign: "middle", margin: 0,
  });

  const rows = [
    ["H1", "Gq → IP3/Ca²⁺", "Endothelium, smooth muscle, nerves", "Vasodilation (via NO), bronchoconstriction, itch, pain, ↑vascular permeability"],
    ["H2", "Gs → ↑cAMP", "Gastric mucosa, cardiac muscle, immune cells", "↑Gastric acid secretion, positive inotropy, vasodilation (high dose)"],
    ["H3", "Gi → ↓cAMP, ↓Ca²⁺", "Presynaptic CNS & peripheral nerves", "Autoreceptor — inhibits release of histamine, ACh, amines, peptides"],
    ["H4", "Gi", "Bone marrow, circulating leukocytes", "Chemotaxis of eosinophils & mast cells; cytokine modulation; allergy"],
  ];
  const rowColors = [C.navyLight, C.navyMid, C.navyLight, C.navyMid];
  const accents   = [C.amber,    C.orange,   C.amber,    C.orange];

  rows.forEach((row, i) => {
    const y = 2.42 + i * 0.62;
    s.addShape(pres.shapes.RECTANGLE, { x: 0.25, y, w: 9.5, h: 0.59, fill: { color: rowColors[i] }, line: { color: rowColors[i], pt: 0 } });
    accentBar(s, 0.25, y, 0.59, accents[i]);
    // H receptor badge
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, {
      x: 0.38, y: y + 0.12, w: 0.45, h: 0.34, rectRadius: 0.05,
      fill: { color: accents[i] }, line: { color: accents[i], pt: 0 },
    });
    s.addText(row[0], { x: 0.38, y: y + 0.12, w: 0.45, h: 0.34, fontSize: 10, bold: true, color: C.navy, align: "center", valign: "middle", margin: 0 });
    s.addText(row[1], { x: 0.9,  y, w: 1.7, h: 0.59, fontSize: 9,   color: C.teal,    valign: "middle" });
    s.addText(row[2], { x: 2.65, y, w: 3.0, h: 0.59, fontSize: 9,   color: C.lightGray, valign: "middle" });
    s.addText(row[3], { x: 5.7,  y, w: 4.0, h: 0.59, fontSize: 9,   color: C.offWhite,  valign: "middle" });
  });
}

// ─────────────────────────────────────────────────────────────────
// SLIDE 4 — SEROTONIN (5-HT)
// ─────────────────────────────────────────────────────────────────
{
  const s = pres.addSlide();
  s.background = { color: C.navy };

  sectionBar(s, "AMINE-DERIVED  |  SEROTONIN  (5-Hydroxytryptamine, 5-HT)", C.amber);

  // Left column - synthesis
  card(s, 0.2, 0.65, 4.6, 1.5, C.navyLight, C.amber);
  s.addText("SYNTHESIS & DISTRIBUTION", { x: 0.32, y: 0.68, w: 4.35, h: 0.28, fontSize: 10, bold: true, color: C.amber });
  s.addText(
    "L-Tryptophan → [Tryptophan hydroxylase ★ rate-limiting] → 5-HTP\n5-HTP → [Aromatic AADC] → Serotonin (5-HT)\n\nDistribution: Gut enterochromaffin (~90%) · Platelets · CNS raphe nuclei\nMetabolism: MAO-A → 5-HIAA (urine)",
    { x: 0.32, y: 0.98, w: 4.35, h: 1.1, fontSize: 9.5, color: C.offWhite }
  );

  // Right column - clinical relevance
  card(s, 5.05, 0.65, 4.7, 1.5, C.navyLight, C.orange);
  s.addText("CLINICAL CONNECTIONS", { x: 5.15, y: 0.68, w: 4.5, h: 0.28, fontSize: 10, bold: true, color: C.orange });
  s.addText(
    "↑ Urinary 5-HIAA → carcinoid syndrome marker\nSSRIs/SNRIs → ↑synaptic 5-HT → antidepressant\nSerotonin syndrome: hyperthermia, clonus, agitation\nCarcinoid tumour: flushing, diarrhoea, bronchospasm",
    { x: 5.15, y: 0.98, w: 4.5, h: 1.1, fontSize: 9.5, color: C.offWhite }
  );

  // Receptor table
  s.addShape(pres.shapes.RECTANGLE, {
    x: 0.2, y: 2.28, w: 9.6, h: 0.34,
    fill: { color: C.amber }, line: { color: C.amber, pt: 0 },
  });
  s.addText("RECEPTOR  |  TYPE / COUPLING  |  LOCATION  |  EFFECTS & DRUGS", {
    x: 0.3, y: 2.28, w: 9.5, h: 0.34, fontSize: 10, bold: true, color: C.navy, valign: "middle", margin: 0,
  });

  const sRows = [
    ["5-HT1A", "Gi → ↓cAMP", "CNS raphe (autoreceptor), limbic", "Anxiolysis, mood; Agonist: buspirone (anxiolytic)"],
    ["5-HT1B/D", "Gi → ↓cAMP", "Cranial blood vessels, presynaptic", "Vasoconstriction; Agonists: TRIPTANS (migraine)"],
    ["5-HT2A", "Gq → IP3/Ca²⁺", "Platelets, blood vessels, CNS", "Vasoconstriction, platelet aggregation; blocked by atypical antipsychotics"],
    ["5-HT3", "Ligand-gated Na⁺/K⁺ ion channel", "Area postrema (CTZ), gut", "Emesis; Antagonists: ondansetron (anti-emetic)"],
    ["5-HT4", "Gs → ↑cAMP", "GI smooth muscle, CNS", "↑Gut motility; Agonists: metoclopramide, prucalopride"],
  ];

  sRows.forEach((row, i) => {
    const y = 2.62 + i * 0.57;
    const bg = i % 2 === 0 ? C.navyLight : C.navyMid;
    s.addShape(pres.shapes.RECTANGLE, { x: 0.2, y, w: 9.6, h: 0.54, fill: { color: bg }, line: { color: bg, pt: 0 } });
    accentBar(s, 0.2, y, 0.54, C.amber);
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, {
      x: 0.32, y: y + 0.1, w: 0.9, h: 0.33, rectRadius: 0.05,
      fill: { color: C.amber }, line: { color: C.amber, pt: 0 },
    });
    s.addText(row[0], { x: 0.32, y: y + 0.1, w: 0.9, h: 0.33, fontSize: 9, bold: true, color: C.navy, align: "center", valign: "middle", margin: 0 });
    s.addText(row[1], { x: 1.28, y, w: 2.0, h: 0.54, fontSize: 8.5, color: C.teal,    valign: "middle" });
    s.addText(row[2], { x: 3.33, y, w: 2.4, h: 0.54, fontSize: 8.5, color: C.lightGray, valign: "middle" });
    s.addText(row[3], { x: 5.78, y, w: 4.0, h: 0.54, fontSize: 8.5, color: C.offWhite,  valign: "middle" });
  });
}

// ─────────────────────────────────────────────────────────────────
// SLIDE 5 — PEPTIDE AUTOCOIDS: BRADYKININ
// ─────────────────────────────────────────────────────────────────
{
  const s = pres.addSlide();
  s.background = { color: C.navy };

  sectionBar(s, "PEPTIDE-DERIVED  |  BRADYKININ & THE KALLIKREIN-KININ SYSTEM", C.green);

  // Pathway flow
  const flowItems = [
    { label: "Prekallikrein", sub: "(activated by FXIIa)", color: C.navyLight, accent: C.teal },
    { label: "Kallikrein", sub: "Plasma / Tissue", color: C.navyLight, accent: C.green },
    { label: "Kininogens", sub: "HMW / LMW", color: C.navyLight, accent: C.teal },
    { label: "Bradykinin", sub: "9-aa peptide", color: C.green, accent: C.white },
  ];

  flowItems.forEach((item, i) => {
    const x = 0.2 + i * 2.42;
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, {
      x, y: 0.65, w: 2.2, h: 0.9, rectRadius: 0.08,
      fill: { color: item.color }, line: { color: item.accent, pt: 1.2 },
    });
    s.addText(item.label, { x, y: 0.68, w: 2.2, h: 0.5, fontSize: 11, bold: true, color: item.accent, align: "center", valign: "middle" });
    s.addText(item.sub, { x, y: 1.1, w: 2.2, h: 0.3, fontSize: 8.5, color: C.gray, align: "center" });
    if (i < 3) {
      s.addText("→", { x: x + 2.2, y: 0.7, w: 0.22, h: 0.7, fontSize: 20, color: C.teal, align: "center", valign: "middle" });
    }
  });

  // Kininase note
  s.addShape(pres.shapes.RECTANGLE, {
    x: 0.2, y: 1.65, w: 9.6, h: 0.52,
    fill: { color: C.navyLight }, line: { color: C.red, pt: 1 },
  });
  s.addText([
    { text: "Kininase II = ACE (Angiotensin Converting Enzyme)", options: { bold: true, color: C.red } },
    { text: " — inactivates bradykinin by cleaving C-terminal dipeptide. ", options: { color: C.offWhite } },
    { text: "ACE inhibitors block this → ↑bradykinin → antihypertensive benefit + ACE-inhibitor cough!", options: { color: C.amber } },
  ], { x: 0.35, y: 1.65, w: 9.3, h: 0.52, fontSize: 10, valign: "middle" });

  // Two receptor cards
  card(s, 0.2, 2.3, 4.6, 1.2, C.navyLight, C.green);
  s.addShape(pres.shapes.RECTANGLE, { x: 0.2, y: 2.3, w: 4.6, h: 0.32, fill: { color: C.green }, line: { color: C.green, pt: 0 } });
  s.addText("B2 RECEPTOR (constitutive)", { x: 0.3, y: 2.3, w: 4.4, h: 0.32, fontSize: 10, bold: true, color: C.navy, valign: "middle", margin: 0 });
  s.addText("Mediates most physiological actions\n• Vasodilation (via NO + prostacyclin)\n• ↑Vascular permeability  •  Pain (sensitises nociceptors)\n• Bronchoconstriction  •  Uterine contraction", {
    x: 0.3, y: 2.65, w: 4.4, h: 0.8, fontSize: 9.5, color: C.offWhite,
  });

  card(s, 5.0, 2.3, 4.8, 1.2, C.navyLight, C.orange);
  s.addShape(pres.shapes.RECTANGLE, { x: 5.0, y: 2.3, w: 4.8, h: 0.32, fill: { color: C.orange }, line: { color: C.orange, pt: 0 } });
  s.addText("B1 RECEPTOR (inducible — upregulated by inflammation)", { x: 5.1, y: 2.3, w: 4.6, h: 0.32, fontSize: 10, bold: true, color: C.navy, valign: "middle", margin: 0 });
  s.addText("Mediates pain and inflammatory responses in sustained/chronic inflammation\nActivated by des-Arg-bradykinin (kinin metabolite)\nTarget for novel analgesic/anti-inflammatory agents", {
    x: 5.1, y: 2.65, w: 4.6, h: 0.8, fontSize: 9.5, color: C.offWhite,
  });

  // Clinical box
  card(s, 0.2, 3.65, 9.6, 1.75, C.navyLight, C.red);
  s.addShape(pres.shapes.RECTANGLE, { x: 0.2, y: 3.65, w: 9.6, h: 0.32, fill: { color: C.red }, line: { color: C.red, pt: 0 } });
  s.addText("CLINICAL RELEVANCE", { x: 0.3, y: 3.65, w: 9.4, h: 0.32, fontSize: 10, bold: true, color: C.white, valign: "middle", margin: 0 });
  s.addText([
    { text: "ACE inhibitor cough: ", options: { bold: true, color: C.amber } },
    { text: "bradykinin accumulation stimulates airway sensory fibres\n", options: { color: C.offWhite } },
    { text: "Hereditary angioedema: ", options: { bold: true, color: C.amber } },
    { text: "C1-INH deficiency → uncontrolled kinin generation → Rx with icatibant (B2 blocker), ecallantide (kallikrein inhibitor), C1-INH concentrate\n", options: { color: C.offWhite } },
    { text: "Carboxypeptidase N (Kininase I): ", options: { bold: true, color: C.teal } },
    { text: "removes C-terminal Arg of bradykinin", options: { color: C.offWhite } },
  ], { x: 0.35, y: 4.0, w: 9.2, h: 1.3, fontSize: 9.5, valign: "top" });
}

// ─────────────────────────────────────────────────────────────────
// SLIDE 6 — NATRIURETIC PEPTIDES & OTHERS
// ─────────────────────────────────────────────────────────────────
{
  const s = pres.addSlide();
  s.background = { color: C.navy };

  sectionBar(s, "PEPTIDE-DERIVED  |  NATRIURETIC PEPTIDES, SUBSTANCE P & ENDOTHELINS", C.green);

  // ── Natriuretic Peptides ──
  s.addText("Natriuretic Peptides", { x: 0.3, y: 0.66, w: 4, h: 0.3, fontSize: 13, bold: true, color: C.green });

  const npRows = [
    ["ANP", "Atria", "Atrial stretch", "Natriuresis, diuresis, vasodilation, ↓RAAS"],
    ["BNP", "Ventricles", "Wall stress", "Same as ANP; biomarker for heart failure (NT-proBNP)"],
    ["CNP", "Endothelium", "Shear stress", "Vasodilation; less natriuretic; CNS effects"],
  ];

  s.addShape(pres.shapes.RECTANGLE, {
    x: 0.25, y: 1.0, w: 4.9, h: 0.3,
    fill: { color: C.green }, line: { color: C.green, pt: 0 },
  });
  s.addText("PEPTIDE  |  SOURCE  |  TRIGGER  |  ACTIONS", {
    x: 0.3, y: 1.0, w: 4.8, h: 0.3, fontSize: 8.5, bold: true, color: C.navy, valign: "middle", margin: 0,
  });
  npRows.forEach((r, i) => {
    const y = 1.3 + i * 0.52;
    const bg = i % 2 === 0 ? C.navyLight : C.navyMid;
    s.addShape(pres.shapes.RECTANGLE, { x: 0.25, y, w: 4.9, h: 0.5, fill: { color: bg }, line: { color: bg, pt: 0 } });
    accentBar(s, 0.25, y, 0.5, C.green);
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.35, y: y + 0.08, w: 0.55, h: 0.32, rectRadius: 0.05, fill: { color: C.green }, line: { color: C.green, pt: 0 } });
    s.addText(r[0], { x: 0.35, y: y + 0.08, w: 0.55, h: 0.32, fontSize: 9, bold: true, color: C.navy, align: "center", valign: "middle", margin: 0 });
    s.addText(r[1], { x: 0.97, y, w: 0.75, h: 0.5, fontSize: 8.5, color: C.teal, valign: "middle" });
    s.addText(r[2], { x: 1.74, y, w: 0.95, h: 0.5, fontSize: 8.5, color: C.lightGray, valign: "middle" });
    s.addText(r[3], { x: 2.72, y, w: 2.38, h: 0.5, fontSize: 8.5, color: C.offWhite, valign: "middle" });
  });

  s.addText("Mechanism: guanylyl cyclase receptor → ↑cGMP → vasodilation + natriuresis\nClinical: nesiritide (rBNP) for acute heart failure; NT-proBNP as diagnostic biomarker", {
    x: 0.25, y: 2.9, w: 4.9, h: 0.6, fontSize: 9, color: C.gray, italic: true,
  });

  // ── Substance P ──
  card(s, 5.35, 0.65, 4.4, 1.5, C.navyLight, C.purple);
  s.addShape(pres.shapes.RECTANGLE, { x: 5.35, y: 0.65, w: 4.4, h: 0.32, fill: { color: C.purple }, line: { color: C.purple, pt: 0 } });
  s.addText("SUBSTANCE P", { x: 5.45, y: 0.65, w: 4.2, h: 0.32, fontSize: 11, bold: true, color: C.white, valign: "middle", margin: 0 });
  s.addText([
    { text: "Structure: ", options: { bold: true, color: C.purple } },
    { text: "Undecapeptide (11 amino acids); tachykinin family\n", options: { color: C.offWhite } },
    { text: "Source: ", options: { bold: true, color: C.purple } },
    { text: "Primary afferent C-fibres, CNS\n", options: { color: C.offWhite } },
    { text: "Receptor: ", options: { bold: true, color: C.purple } },
    { text: "NK1 (neurokinin-1), Gq-coupled\n", options: { color: C.offWhite } },
    { text: "Actions: ", options: { bold: true, color: C.purple } },
    { text: "Pain transmission, neurogenic inflammation, vasodilation, ↑vascular permeability", options: { color: C.offWhite } },
  ], { x: 5.45, y: 1.0, w: 4.2, h: 1.1, fontSize: 9.5 });

  // ── Endothelins ──
  card(s, 5.35, 2.32, 4.4, 2.1, C.navyLight, C.red);
  s.addShape(pres.shapes.RECTANGLE, { x: 5.35, y: 2.32, w: 4.4, h: 0.32, fill: { color: C.red }, line: { color: C.red, pt: 0 } });
  s.addText("ENDOTHELINS", { x: 5.45, y: 2.32, w: 4.2, h: 0.32, fontSize: 11, bold: true, color: C.white, valign: "middle", margin: 0 });
  s.addText([
    { text: "3 isoforms: ", options: { bold: true, color: C.red } },
    { text: "ET-1 (main), ET-2, ET-3 — 21 aa peptides\n", options: { color: C.offWhite } },
    { text: "Source: ", options: { bold: true, color: C.red } },
    { text: "Vascular endothelium, heart, kidney\n", options: { color: C.offWhite } },
    { text: "Synthesis: ", options: { bold: true, color: C.red } },
    { text: "Preproendothelin → Big ET-1 → [ECE] → ET-1\n", options: { color: C.offWhite } },
    { text: "ETA: ", options: { bold: true, color: C.amber } },
    { text: "vasoconstriction, smooth muscle proliferation\n", options: { color: C.offWhite } },
    { text: "ETB: ", options: { bold: true, color: C.teal } },
    { text: "vasodilation via NO; endothelial clearance of ET-1\n", options: { color: C.offWhite } },
    { text: "ET-1 = most potent endogenous vasoconstrictor known\n", options: { bold: true, color: C.amber } },
    { text: "Rx: bosentan/ambrisentan (ETA/ETB blockers) → pulmonary arterial hypertension", options: { color: C.offWhite } },
  ], { x: 5.45, y: 2.67, w: 4.2, h: 1.7, fontSize: 9.5 });

  // Bottom note
  s.addText("Also: Angiotensin II (vasoconstriction, ↑aldosterone) and neuropeptide Y (NPY) are classified as peptide autocoids/paracoids in many contexts", {
    x: 0.25, y: 5.2, w: 9.5, h: 0.3, fontSize: 8.5, color: C.gray, italic: true, align: "center",
  });
}

// ─────────────────────────────────────────────────────────────────
// SLIDE 7 — LIPID AUTOCOIDS: EICOSANOID PATHWAY OVERVIEW
// ─────────────────────────────────────────────────────────────────
{
  const s = pres.addSlide();
  s.background = { color: C.navy };

  sectionBar(s, "LIPID-DERIVED  |  EICOSANOIDS — BIOSYNTHETIC PATHWAYS", C.purple);

  // Central precursor box
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, {
    x: 3.6, y: 0.65, w: 2.8, h: 0.8, rectRadius: 0.1,
    fill: { color: C.navyLight }, line: { color: C.white, pt: 1.5 },
  });
  s.addText("Membrane Phospholipids", { x: 3.6, y: 0.67, w: 2.8, h: 0.38, fontSize: 10, bold: true, color: C.white, align: "center" });
  s.addText("↓ Phospholipase A2 (PLA2)\n[Corticosteroids inhibit via lipocortin]", {
    x: 3.6, y: 1.0, w: 2.8, h: 0.38, fontSize: 8.5, color: C.gray, align: "center",
  });

  // AA box
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, {
    x: 3.9, y: 1.55, w: 2.2, h: 0.55, rectRadius: 0.08,
    fill: { color: C.purple }, line: { color: C.purple, pt: 0 },
  });
  s.addText("ARACHIDONIC ACID (AA)", { x: 3.9, y: 1.55, w: 2.2, h: 0.55, fontSize: 9.5, bold: true, color: C.white, align: "center", valign: "middle" });

  // Connector
  s.addShape(pres.shapes.RECTANGLE, { x: 4.95, y: 1.44, w: 0.1, h: 0.12, fill: { color: C.white }, line: { color: C.white, pt: 0 } });

  // ── COX PATHWAY ──
  card(s, 0.2, 2.22, 3.0, 3.1, C.navyLight, C.teal);
  s.addShape(pres.shapes.RECTANGLE, { x: 0.2, y: 2.22, w: 3.0, h: 0.38, fill: { color: C.teal }, line: { color: C.teal, pt: 0 } });
  s.addText("COX PATHWAY", { x: 0.3, y: 2.22, w: 2.8, h: 0.38, fontSize: 11, bold: true, color: C.navy, valign: "middle", margin: 0 });
  s.addText("Enzyme: Cyclooxygenase-1 (constitutive)\n          Cyclooxygenase-2 (inducible)\nInhibited by: NSAIDs / Aspirin\n\n→ PGG2 → PGH2 (precursor)\n\n• PGE2: fever, vasodilation, pain\n• PGI2 (prostacyclin): vasodilation, ↓platelets\n• TxA2: vasoconstriction, ↑platelets\n• PGD2: bronchoconstriction, sleep\n• PGF2α: uterine contraction", {
    x: 0.3, y: 2.65, w: 2.8, h: 2.6, fontSize: 9.5, color: C.offWhite,
  });

  // ── LOX PATHWAY ──
  card(s, 3.5, 2.22, 3.0, 3.1, C.navyLight, C.orange);
  s.addShape(pres.shapes.RECTANGLE, { x: 3.5, y: 2.22, w: 3.0, h: 0.38, fill: { color: C.orange }, line: { color: C.orange, pt: 0 } });
  s.addText("LOX PATHWAY", { x: 3.6, y: 2.22, w: 2.8, h: 0.38, fontSize: 11, bold: true, color: C.navy, valign: "middle", margin: 0 });
  s.addText("Enzyme: 5-Lipoxygenase (5-LOX)\nActivated by: FLAP protein\nInhibited by: Zileuton\n\n→ 5-HPETE → LTA4\n\n• LTB4: neutrophil chemotaxis\n• LTC4/D4/E4 (cysteinyl-LTs)\n  = bronchoconstriction, ↑mucus,\n  ↑vascular permeability\n• Lipoxins: anti-inflammatory signals", {
    x: 3.6, y: 2.65, w: 2.8, h: 2.6, fontSize: 9.5, color: C.offWhite,
  });

  // ── CYP PATHWAY ──
  card(s, 6.8, 2.22, 3.0, 3.1, C.navyLight, C.red);
  s.addShape(pres.shapes.RECTANGLE, { x: 6.8, y: 2.22, w: 3.0, h: 0.38, fill: { color: C.red }, line: { color: C.red, pt: 0 } });
  s.addText("CYP PATHWAY", { x: 6.9, y: 2.22, w: 2.8, h: 0.38, fontSize: 11, bold: true, color: C.white, valign: "middle", margin: 0 });
  s.addText("Enzyme: Cytochrome P450\nEpoxidase / ω-hydroxylase\n\n→ EETs (epoxyeicosatrienoic acids)\n→ HETEs (hydroxyeicosatetraenoic acids)\n\n• Vasodilation (EETs)\n• Renal tubular ion transport\n• ↑Cell proliferation\n• Less pharmacologically targeted\n  than COX/LOX", {
    x: 6.9, y: 2.65, w: 2.8, h: 2.6, fontSize: 9.5, color: C.offWhite,
  });

  // Arrow from AA to each pathway
  s.addShape(pres.shapes.RECTANGLE, { x: 1.65, y: 2.1, w: 0.08, h: 0.13, fill: { color: C.teal }, line: { color: C.teal, pt: 0 } });
  s.addShape(pres.shapes.RECTANGLE, { x: 4.92, y: 2.1, w: 0.08, h: 0.13, fill: { color: C.orange }, line: { color: C.orange, pt: 0 } });
  s.addShape(pres.shapes.RECTANGLE, { x: 8.25, y: 2.1, w: 0.08, h: 0.13, fill: { color: C.red }, line: { color: C.red, pt: 0 } });
}

// ─────────────────────────────────────────────────────────────────
// SLIDE 8 — PROSTANOIDS IN DETAIL
// ─────────────────────────────────────────────────────────────────
{
  const s = pres.addSlide();
  s.background = { color: C.navy };

  sectionBar(s, "LIPID-DERIVED  |  PROSTANOIDS (COX Pathway Products)", C.teal);

  // COX-1 vs COX-2 mini cards
  card(s, 0.2, 0.65, 4.6, 0.95, C.navyLight, C.teal);
  s.addText([
    { text: "COX-1 (constitutive): ", options: { bold: true, color: C.teal } },
    { text: "Housekeeping — gastric cytoprotection (PGE2/PGI2), platelet TxA2, renal homeostasis. Inhibited by non-selective NSAIDs & aspirin.", options: { color: C.offWhite } },
  ], { x: 0.35, y: 0.68, w: 4.3, h: 0.89, fontSize: 9.5, valign: "middle" });

  card(s, 5.0, 0.65, 4.8, 0.95, C.navyLight, C.orange);
  s.addText([
    { text: "COX-2 (inducible): ", options: { bold: true, color: C.orange } },
    { text: "Upregulated by cytokines, shear stress, growth factors. Source of inflammatory prostanoids. Selectively inhibited by coxibs (celecoxib, etoricoxib). Also constitutive in kidney & brain.", options: { color: C.offWhite } },
  ], { x: 5.15, y: 0.68, w: 4.5, h: 0.89, fontSize: 9.5, valign: "middle" });

  // Table
  s.addShape(pres.shapes.RECTANGLE, {
    x: 0.2, y: 1.73, w: 9.6, h: 0.34,
    fill: { color: C.teal }, line: { color: C.teal, pt: 0 },
  });
  s.addText("PROSTANOID  |  MAIN SOURCE  |  RECEPTOR  |  KEY ACTIONS  |  CLINICAL USE", {
    x: 0.3, y: 1.73, w: 9.5, h: 0.34, fontSize: 9.5, bold: true, color: C.navy, valign: "middle", margin: 0,
  });

  const pRows = [
    ["PGE2", "Many tissues (COX-2)", "EP1-EP4", "Vasodilation, fever (hypothalamus), pain sensitisation, uterine contraction, gastric cytoprotection", "Misoprostol (PGE1 analog) — ulcer Rx, cervical ripening"],
    ["PGI2\n(Prostacyclin)", "Vascular endothelium", "IP (Gs→↑cAMP)", "Potent vasodilation, inhibits platelet aggregation, renal vasodilation — OPPOSES TxA2", "Epoprostenol, iloprost — pulmonary arterial hypertension"],
    ["TxA2", "Platelets (COX-1)", "TP (Gq)", "Potent vasoconstriction, platelet aggregation, bronchoconstriction. Short t½ (<30 sec)", "Aspirin inhibits COX-1 irreversibly → antiplatelet"],
    ["PGD2", "Mast cells, brain", "DP1, DP2", "Vasodilation, bronchoconstriction, eosinophil chemotaxis, sleep regulation", "DP2 (CRTH2) antagonists in asthma (investigational)"],
    ["PGF2α", "Uterus, lungs", "FP (Gq)", "Uterine contraction, luteolysis, bronchoconstriction, ↑IOP", "Latanoprost (FP agonist) → glaucoma; dinoprostone → labour"],
  ];
  const rowBgs = [C.navyLight, C.navyMid, C.navyLight, C.navyMid, C.navyLight];
  pRows.forEach((row, i) => {
    const y = 2.07 + i * 0.63;
    s.addShape(pres.shapes.RECTANGLE, { x: 0.2, y, w: 9.6, h: 0.6, fill: { color: rowBgs[i] }, line: { color: rowBgs[i], pt: 0 } });
    accentBar(s, 0.2, y, 0.6, C.teal);
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.32, y: y + 0.1, w: 0.95, h: 0.38, rectRadius: 0.05, fill: { color: C.teal }, line: { color: C.teal, pt: 0 } });
    s.addText(row[0], { x: 0.32, y: y + 0.1, w: 0.95, h: 0.38, fontSize: 8.5, bold: true, color: C.navy, align: "center", valign: "middle", margin: 0 });
    s.addText(row[1], { x: 1.33, y, w: 1.45, h: 0.6, fontSize: 8.5, color: C.teal,    valign: "middle" });
    s.addText(row[2], { x: 2.82, y, w: 1.1,  h: 0.6, fontSize: 8.5, color: C.lightGray, valign: "middle" });
    s.addText(row[3], { x: 3.96, y, w: 3.3,  h: 0.6, fontSize: 8.5, color: C.offWhite,  valign: "middle" });
    s.addText(row[4], { x: 7.3,  y, w: 2.45, h: 0.6, fontSize: 8,   color: C.amber,     valign: "middle" });
  });
}

// ─────────────────────────────────────────────────────────────────
// SLIDE 9 — LEUKOTRIENES, LIPOXINS & PAF
// ─────────────────────────────────────────────────────────────────
{
  const s = pres.addSlide();
  s.background = { color: C.navy };

  sectionBar(s, "LIPID-DERIVED  |  LEUKOTRIENES · LIPOXINS · PAF", C.orange);

  // Leukotrienes section
  card(s, 0.2, 0.65, 5.65, 2.85, C.navyLight, C.orange);
  s.addShape(pres.shapes.RECTANGLE, { x: 0.2, y: 0.65, w: 5.65, h: 0.34, fill: { color: C.orange }, line: { color: C.orange, pt: 0 } });
  s.addText("LEUKOTRIENES (5-LOX Pathway)", { x: 0.3, y: 0.65, w: 5.5, h: 0.34, fontSize: 11, bold: true, color: C.navy, valign: "middle", margin: 0 });

  s.addText([
    { text: "AA → 5-HPETE → LTA4 (unstable epoxide)\n", options: { color: C.teal, bold: true } },
    { text: "           ↓ LTA4 hydrolase              ↓ LTC4 synthase + glutathione\n", options: { color: C.gray } },
    { text: "         LTB4                               LTC4 → LTD4 → LTE4\n", options: { color: C.offWhite } },
  ], { x: 0.32, y: 1.03, w: 5.45, h: 0.65, fontSize: 9.5 });

  const ltRows = [
    { name: "LTB4",     color: C.orange, desc: "Potent neutrophil chemotaxis & adhesion; promotes acute inflammation; activates BLT1/BLT2 receptors" },
    { name: "LTC4/D4/E4", color: C.red, desc: "Cysteinyl-LTs (SRS-A) — 1000× more potent than histamine for bronchoconstriction; ↑mucus; ↑vascular permeability → asthma, anaphylaxis" },
    { name: "Lipoxins\nLXA4/LXB4", color: C.green, desc: "Anti-inflammatory 'stop signals' — inhibit neutrophil recruitment, promote resolution of inflammation; formed by 15-LOX + 5-LOX cooperation" },
  ];
  ltRows.forEach((r, i) => {
    const y = 1.72 + i * 0.56;
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x: 0.32, y: y + 0.05, w: 1.1, h: 0.44, rectRadius: 0.06, fill: { color: r.color }, line: { color: r.color, pt: 0 } });
    s.addText(r.name, { x: 0.32, y: y + 0.05, w: 1.1, h: 0.44, fontSize: 8.5, bold: true, color: C.navy, align: "center", valign: "middle", margin: 0 });
    s.addText(r.desc, { x: 1.5, y, w: 4.2, h: 0.54, fontSize: 9, color: C.offWhite, valign: "middle" });
  });

  // Drug box inside leukotriene card
  s.addShape(pres.shapes.RECTANGLE, { x: 0.32, y: 3.2, w: 5.45, h: 0.24, fill: { color: "102040" }, line: { color: "102040", pt: 0 } });
  s.addText([
    { text: "Drugs: ", options: { bold: true, color: C.amber } },
    { text: "Montelukast, zafirlukast (CysLT1 blockers) — asthma/rhinitis  |  Zileuton (5-LOX inhibitor) — asthma", options: { color: C.offWhite } },
  ], { x: 0.35, y: 3.2, w: 5.4, h: 0.24, fontSize: 8.5, valign: "middle" });

  // PAF section
  card(s, 6.1, 0.65, 3.7, 4.7, C.navyLight, C.red);
  s.addShape(pres.shapes.RECTANGLE, { x: 6.1, y: 0.65, w: 3.7, h: 0.34, fill: { color: C.red }, line: { color: C.red, pt: 0 } });
  s.addText("PLATELET-ACTIVATING FACTOR (PAF)", { x: 6.2, y: 0.65, w: 3.5, h: 0.34, fontSize: 10, bold: true, color: C.white, valign: "middle", margin: 0 });

  s.addText([
    { text: "Structure: ", options: { bold: true, color: C.red } },
    { text: "1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (acetylated phospholipid)\n\n", options: { color: C.offWhite } },
    { text: "Sources: ", options: { bold: true, color: C.red } },
    { text: "Platelets, mast cells, neutrophils, monocytes, vascular endothelium\n\n", options: { color: C.offWhite } },
    { text: "Receptor: ", options: { bold: true, color: C.red } },
    { text: "PAF-R (PAFR) — GPCR (Gi/Gq)\n\n", options: { color: C.offWhite } },
    { text: "Key Actions:\n", options: { bold: true, color: C.amber } },
    { text: "• Platelet aggregation & activation\n• Potent bronchoconstriction\n• Vasoconstriction (low dose) / vasodilation (high dose)\n• ↑Vascular permeability\n• Leukocyte chemotaxis & activation\n• Key mediator in anaphylaxis & severe sepsis\n\n", options: { color: C.offWhite } },
    { text: "Metabolism: ", options: { bold: true, color: C.teal } },
    { text: "Rapidly inactivated by PAF-acetylhydrolase (PAF-AH)\n\n", options: { color: C.offWhite } },
    { text: "Note: ", options: { bold: true, color: C.amber } },
    { text: "PAF-AH deficiency is associated with severe asthma in children", options: { color: C.offWhite } },
  ], { x: 6.2, y: 1.04, w: 3.5, h: 4.2, fontSize: 9.5 });
}

// ─────────────────────────────────────────────────────────────────
// SLIDE 10 — PHARMACOLOGY & DRUG SUMMARY
// ─────────────────────────────────────────────────────────────────
{
  const s = pres.addSlide();
  s.background = { color: C.navy };

  sectionBar(s, "PHARMACOLOGICAL TARGETS — DRUGS ACTING ON AUTOCOID PATHWAYS", C.teal);

  const drugs = [
    { cat: "H1 Blockers", color: C.amber, drugs: "1st gen: diphenhydramine, promethazine, chlorpheniramine\n2nd gen: cetirizine, loratadine, fexofenadine (no sedation)\nUse: allergy, urticaria, motion sickness, anaphylaxis (adjunct)" },
    { cat: "H2 Blockers", color: C.orange, drugs: "Ranitidine, famotidine, cimetidine\nUse: peptic ulcer, GERD, Zollinger-Ellison syndrome" },
    { cat: "5-HT Drugs", color: C.purple, drugs: "Triptans (5-HT1B/D agonist): sumatriptan — migraine\nSSRIs/SNRIs: fluoxetine, venlafaxine — depression\nOndansetron (5-HT3 antagonist): chemo nausea\nBuspirone (5-HT1A partial agonist): anxiety" },
    { cat: "ACE Inhibitors\n(↑Bradykinin)", color: C.green, drugs: "Enalapril, lisinopril, ramipril\nBenefit: ↑bradykinin → vasodilation, renal protection\nSide effect: dry cough (bradykinin accumulation → tachykinins → airway irritation)" },
    { cat: "Eicosanoid\nTargets", color: C.teal, drugs: "NSAIDs (COX-1+2): ibuprofen, naproxen — anti-inflammatory, analgesic\nAspirin (COX-1 irreversible): antiplatelet\nCoxibs (COX-2): celecoxib — arthritis (↑CV risk)\nMontelukast (CysLT1): asthma\nLatanoprost (PGF2α): glaucoma\nEpoprostenol (PGI2): PAH" },
    { cat: "Corticosteroids\n(Master inhibitor)", color: C.red, drugs: "↑Lipocortin → ↓PLA2 → blocks ALL eicosanoid pathways\nDexamethasone, prednisolone — anti-inflammatory, anaphylaxis" },
  ];

  const cols = [0, 1, 0, 1, 0, 1];
  const rows = [0, 0, 1, 1, 2, 2];
  const xStart = [0.2, 5.0];
  const yStart = [0.65, 2.38, 4.1];
  const cardW = 4.65;
  const cardH = 1.55;

  drugs.forEach((d, i) => {
    const x = xStart[cols[i]];
    const y = yStart[rows[i]];
    card(s, x, y, cardW, cardH, C.navyLight, d.color);
    s.addShape(pres.shapes.RECTANGLE, { x, y, w: cardW, h: 0.3, fill: { color: d.color }, line: { color: d.color, pt: 0 } });
    s.addText(d.cat, { x: x + 0.1, y, w: cardW - 0.15, h: 0.3, fontSize: 10, bold: true, color: i === 2 ? C.white : C.navy, valign: "middle", margin: 0 });
    s.addText(d.drugs, { x: x + 0.12, y: y + 0.33, w: cardW - 0.2, h: 1.18, fontSize: 8.8, color: C.offWhite, valign: "top" });
  });
}

// ─────────────────────────────────────────────────────────────────
// SLIDE 11 — SUMMARY TABLE
// ─────────────────────────────────────────────────────────────────
{
  const s = pres.addSlide();
  s.background = { color: C.navy };

  sectionBar(s, "SUMMARY TABLE — AUTOCOIDS AT A GLANCE", C.teal);

  const thead = [
    [
      { text: "CLASS",      options: { bold: true, color: C.navy, fill: { color: C.teal } } },
      { text: "AUTOCOID",   options: { bold: true, color: C.navy, fill: { color: C.teal } } },
      { text: "PRECURSOR",  options: { bold: true, color: C.navy, fill: { color: C.teal } } },
      { text: "KEY ENZYME", options: { bold: true, color: C.navy, fill: { color: C.teal } } },
      { text: "MAIN ACTIONS", options: { bold: true, color: C.navy, fill: { color: C.teal } } },
    ],
  ];

  const trows = [
    [
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// ─── OUTPUT ────────────────────────────────────────────────────────
pres.writeFile({ fileName: "/home/daytona/workspace/autocoids-pptx/Autocoids_Pharmacology.pptx" })
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Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/autocoids-pptx/autocoids.js'

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/autocoids-pptx/autocoids.js'

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// ══════════════════════════════════════════════════════════════
// SLIDE 1 — TITLE
// ══════════════════════════════════════════════════════════════
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// ══════════════════════════════════════════════════════════════
// SLIDE 2 — HISTAMINE: SYNTHESIS, STORAGE & RELEASE
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    ["H3","Gi → ↓cAMP, ↓Ca²⁺","Presynaptic neurons — CNS & PNS (autoreceptor)","Inhibits release of histamine, ACh, amines, peptides; modulates appetite/satiety"],
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// ══════════════════════════════════════════════════════════════
// SLIDE 3 — HISTAMINE: ORGAN EFFECTS & DRUGS
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    ["2nd Generation","Cetirizine, loratadine, fexofenadine","Do NOT cross BBB → no sedation; minimal autonomic effects; fexofenadine: zero sedation","Allergic rhinitis, urticaria, chronic idiopathic urticaria — preferred"],
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// ══════════════════════════════════════════════════════════════
// SLIDE 4 — SEROTONIN: SYNTHESIS, DISTRIBUTION & RECEPTORS
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    { text:"Aldehyde dehydrogenase  →  5-HIAA ", options:{color:C.offWhite} },
    { text:"(urine)\n", options:{color:C.teal} },
    { text:"↑Urinary 5-HIAA = diagnostic marker for CARCINOID TUMOUR", options:{bold:true, color:C.amber} },
  ], { x:0.38, y:1.87, w:4.45, h:0.62, fontSize:9.5 });

  hdrCard(s, 5.1, 1.52, 4.65, 1.0, "DISTRIBUTION", C.teal);
  s.addText([
    { text:">90%  ", options:{bold:true, color:C.teal} },
    { text:"in GI enterochromaffin cells\n", options:{color:C.offWhite} },
    { text:"Platelets ", options:{bold:true, color:C.teal} },
    { text:"(concentrated via SERT transporter; stored by VAT — blocked by reserpine)\n", options:{color:C.offWhite} },
    { text:"CNS ", options:{bold:true, color:C.teal} },
    { text:"raphe nuclei: mood, sleep, appetite, pain, BP, vomiting\n", options:{color:C.offWhite} },
    { text:"Enteric nervous system ", options:{bold:true, color:C.teal} },
    { text:"— GI motility regulation", options:{color:C.offWhite} },
  ], { x:5.22, y:1.87, w:4.4, h:0.62, fontSize:9.2 });

  // Receptor table
  tblHeader(s, 0.25, 2.62, 9.5, ["Receptor","Coupling","Location","Key Actions","Key Drugs"], [0.92,1.5,2.0,2.88,2.2], C.amber);
  const sRows = [
    ["5-HT1A","Gi→↓cAMP","Raphe nuclei (autoreceptor), limbic","Anxiolysis, mood regulation","Buspirone (partial agonist) — anxiety"],
    ["5-HT1B/D","Gi→↓cAMP","Cranial blood vessels, presynaptic","Cranial vasoconstriction, inhibit trigeminal neuropeptides","Triptans (sumatriptan) — migraine"],
    ["5-HT2A","Gq→↑IP3","Platelets, vascular SM, CNS","Vasoconstriction, platelet aggregation","Blocked by atypical antipsychotics"],
    ["5-HT3","Ion channel\n(Na⁺/K⁺)","Area postrema (CTZ), gut","Emesis, gut motility (only non-GPCR)","Ondansetron — chemo nausea"],
    ["5-HT4","Gs→↑cAMP","GI smooth muscle","↑GI motility","Metoclopramide, prucalopride"],
  ];
  const sBgs = [C.bgLight, C.bgMid, C.bgLight, C.bgMid, C.bgLight];
  sRows.forEach((r, i) => {
    const y = 2.92 + i*0.52;
    tblRow(s, 0.25, y, r, [0.92,1.5,2.0,2.88,2.2], C.amber, sBgs[i]);
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x:0.3, y:y+0.09, w:0.82, h:0.32, rectRadius:0.05, fill:{color:C.amber}, line:{color:C.amber,pt:0} });
    s.addText(r[0], { x:0.3, y:y+0.09, w:0.82, h:0.32, fontSize:8.5, bold:true, color:C.bg, align:"center", valign:"middle", margin:0 });
  });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 5 — PEPTIDE AUTOCOIDS: BRADYKININ
// ══════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color:C.bg };
  topBar(s, "PART II — PEPTIDE-DERIVED AUTOCOIDS  |  BRADYKININ & THE KALLIKREIN-KININ SYSTEM", C.green);

  // Formation cascade
  const cascade = [
    { t:"Prekallikrein", sub:"(activated by FXIIa)" },
    { t:"KALLIKREIN", sub:"Plasma / Tissue types" },
    { t:"Kininogens", sub:"HMW → bradykinin\nLMW → kallidin" },
    { t:"BRADYKININ", sub:"9-amino acid peptide\nt½ < 15 seconds", hi:true },
  ];
  cascade.forEach((c, i) => {
    const x = 0.25 + i*2.38;
    const bc = c.hi ? C.green : C.bgLight;
    const tc = c.hi ? C.bg : C.offWhite;
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x, y:0.6, w:2.18, h:0.88, rectRadius:0.07, fill:{color:bc}, line:{color:C.green,pt:c.hi?0:1.1} });
    s.addText(c.t, { x, y:0.62, w:2.18, h:0.48, fontSize:c.hi?12:10.5, bold:true, color:tc, align:"center", valign:"middle" });
    s.addText(c.sub, { x, y:1.08, w:2.18, h:0.4, fontSize:8.5, color:c.hi?C.bgMid:C.gray, align:"center" });
    if(i<3) s.addText("→", { x:x+2.18, y:0.6, w:0.2, h:0.88, fontSize:22, color:C.green, align:"center", valign:"middle" });
  });

  // ACE/Kininase II callout
  s.addShape(pres.shapes.RECTANGLE, { x:0.25, y:1.57, w:9.5, h:0.52, fill:{color:C.bgMid}, line:{color:C.red,pt:1.2} });
  leftBar(s, 0.25, 1.57, 0.52, C.red);
  s.addText([
    { text:"Kininase II = ACE  ", options:{bold:true, color:C.red} },
    { text:"inactivates bradykinin by cleaving C-terminal Phe-Arg dipeptide (nearly complete degradation in ONE lung passage). ", options:{color:C.offWhite} },
    { text:"ACE inhibitors → ↑bradykinin → vasodilation (antihypertensive benefit) + dry cough (B2 on airway C-fibres).", options:{bold:true, color:C.amber} },
  ], { x:0.38, y:1.57, w:9.25, h:0.52, fontSize:9.5, valign:"middle" });

  // B1 / B2 receptor cards
  hdrCard(s, 0.25, 2.2, 4.6, 1.35, "B2 RECEPTOR (constitutive)", C.green);
  s.addText([
    { text:"Mediates all NORMAL physiological actions:\n", options:{bold:true, color:C.green} },
    { text:"• Vasodilation via endothelial NO + PGI2 release\n", options:{color:C.offWhite} },
    { text:"• ↑Vascular permeability\n• Pain & hyperalgesia (sensitises nociceptors)\n• Bronchoconstriction\n• Uterine contraction\n• Stimulates prostaglandin synthesis", options:{color:C.offWhite} },
  ], { x:0.38, y:2.56, w:4.35, h:0.95, fontSize:9.2, valign:"top" });

  hdrCard(s, 5.1, 2.2, 4.65, 1.35, "B1 RECEPTOR (inducible — upregulated by IL-1, TNF)", C.orange);
  s.addText([
    { text:"Mediates chronic pain & inflammatory responses\n", options:{bold:true, color:C.orange} },
    { text:"• Upregulated during sustained inflammation\n", options:{color:C.offWhite} },
    { text:"• Activated by des-Arg-bradykinin (C-terminal Arg removed metabolite)\n", options:{color:C.offWhite} },
    { text:"• Target for novel analgesic/anti-inflammatory drugs\n", options:{color:C.offWhite} },
    { text:"• SSR240612: selective B1 antagonist (preclinical)", options:{color:C.lt} },
  ], { x:5.22, y:2.56, w:4.45, h:0.95, fontSize:9.2, valign:"top" });

  // Drug table
  tblHeader(s, 0.25, 3.66, 9.5, ["Drug / Agent","Mechanism","Clinical Use"], [2.5,4.0,3.0], C.green);
  const kdrugs = [
    ["ACE inhibitors (enalapril, lisinopril)","Block Kininase II → ↑bradykinin → vasodilation","Hypertension, heart failure, CKD/diabetic nephropathy"],
    ["Icatibant","Bradykinin B2 receptor antagonist","Acute attacks of hereditary angioedema (HAE)"],
    ["Ecallantide","Recombinant plasma kallikrein inhibitor","HAE — acute attacks (SC injection)"],
    ["C1-INH concentrate (Berinert, Cinryze)","Replaces deficient C1-esterase inhibitor → ↓kallikrein activation","HAE — prophylaxis and acute treatment"],
  ];
  const kbgs = [C.bgLight, C.bgMid, C.bgLight, C.bgMid];
  kdrugs.forEach((r, i) => {
    tblRow(s, 0.25, 3.96+i*0.42, r, [2.5,4.0,3.0], C.green, kbgs[i]);
  });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 6 — NATRIURETIC PEPTIDES, ENDOTHELINS & SUBSTANCE P
// ══════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color:C.bg };
  topBar(s, "PART II — NATRIURETIC PEPTIDES  ·  ENDOTHELINS  ·  SUBSTANCE P", C.green);

  // Natriuretic peptides
  hdrCard(s, 0.25, 0.62, 5.55, 2.45, "NATRIURETIC PEPTIDES", C.teal);
  s.addText("Mechanism: bind particulate guanylyl cyclase receptors (GC-A) → ↑cGMP → vasodilation & natriuresis", {
    x:0.38, y:0.98, w:5.3, h:0.35, fontSize:9, color:C.teal, italic:true,
  });
  tblHeader(s, 0.35, 1.38, 5.35, ["Peptide","Source","Stimulus","Key Actions"], [0.65,1.1,1.1,2.5], C.teal);
  const npRows = [
    ["ANP","Atrial myocytes","Atrial stretch, volume expansion","Natriuresis, diuresis, vasodilation, ↓renin, ↓aldosterone, ↓AVP"],
    ["BNP","Ventricular myocytes","Ventricular wall stress (pressure overload)","Same as ANP; biomarker for HF (NT-proBNP diagnostic)"],
    ["CNP","Vascular endothelium","Shear stress, cytokines","Vasodilation; less natriuretic; CNS effects"],
  ];
  const npBgs=[C.bgLight, C.bgMid, C.bgLight];
  npRows.forEach((r,i)=>{
    tblRow(s, 0.35, 1.68+i*0.48, r, [0.65,1.1,1.1,2.5], C.teal, npBgs[i]);
    pill(s, 0.38, 1.68+i*0.48+0.09, 0.56, 0.3, r[0], C.teal, C.bg);
  });
  s.addText([
    { text:"Clinical use: ", options:{bold:true, color:C.amber} },
    { text:"Nesiritide (recombinant BNP) → acute decompensated heart failure", options:{color:C.offWhite} },
  ], { x:0.38, y:2.88, w:5.3, h:0.18, fontSize:9 });

  // Endothelins
  hdrCard(s, 6.05, 0.62, 3.7, 2.45, "ENDOTHELINS (ET-1, ET-2, ET-3)", C.red);
  s.addText([
    { text:"21 amino-acid peptides; ET-1 = most potent endogenous vasoconstrictor\n", options:{bold:true, color:C.red} },
    { text:"Synthesis: ", options:{bold:true, color:C.amber} },
    { text:"Preproendothelin → Big ET-1 → [ECE] → ET-1\n\n", options:{color:C.offWhite} },
    { text:"ETA receptor: ", options:{bold:true, color:C.orange} },
    { text:"Gq → vasoconstriction, SM proliferation\n", options:{color:C.offWhite} },
    { text:"ETB receptor: ", options:{bold:true, color:C.teal} },
    { text:"Gi/Gq → vasodilation (via NO+PGI2); clearance of ET-1 from circulation\n\n", options:{color:C.offWhite} },
    { text:"Drugs: ", options:{bold:true, color:C.amber} },
    { text:"Bosentan, ambrisentan (ETA/B blockers)\n→ Pulmonary arterial hypertension (PAH)", options:{color:C.offWhite} },
  ], { x:6.17, y:0.97, w:3.5, h:2.07, fontSize:9.2 });

  // Substance P
  hdrCard(s, 0.25, 3.18, 5.55, 1.4, "SUBSTANCE P", C.purple);
  s.addText([
    { text:"Structure: ", options:{bold:true, color:C.purple} },
    { text:"Undecapeptide (11 aa); tachykinin family\n", options:{color:C.offWhite} },
    { text:"Source: ", options:{bold:true, color:C.purple} },
    { text:"Primary afferent C-fibres, CNS enteric neurons\n", options:{color:C.offWhite} },
    { text:"Receptor: ", options:{bold:true, color:C.purple} },
    { text:"NK1 (neurokinin-1) — Gq-coupled\n", options:{color:C.offWhite} },
    { text:"Actions: ", options:{bold:true, color:C.purple} },
    { text:"Pain transmission, neurogenic inflammation, vasodilation, emesis\n", options:{color:C.offWhite} },
    { text:"Drug: ", options:{bold:true, color:C.amber} },
    { text:"Aprepitant (NK1 antagonist) → chemotherapy-induced nausea/vomiting", options:{color:C.offWhite} },
  ], { x:0.38, y:3.52, w:5.3, h:1.0, fontSize:9.2 });

  // Angiotensin II note
  hdrCard(s, 6.05, 3.18, 3.7, 1.4, "ANGIOTENSIN II (note)", C.blue);
  s.addText([
    { text:"Also considered a peptide autocoid/hormone\n", options:{color:C.lt, italic:true} },
    { text:"AT1 receptor (Gq): ", options:{bold:true, color:C.blue} },
    { text:"vasoconstriction, aldosterone release, cardiac hypertrophy\n", options:{color:C.offWhite} },
    { text:"AT2 receptor (Gi): ", options:{bold:true, color:C.teal} },
    { text:"vasodilation, anti-proliferative, fetal development\n", options:{color:C.offWhite} },
    { text:"Drugs: ", options:{bold:true, color:C.amber} },
    { text:"ARBs (losartan) — block AT1 without affecting bradykinin (no cough)", options:{color:C.offWhite} },
  ], { x:6.17, y:3.52, w:3.5, h:1.0, fontSize:9.2 });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 7 — LIPID AUTOCOIDS: EICOSANOID PATHWAYS OVERVIEW
// ══════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color:C.bg };
  topBar(s, "PART III — LIPID-DERIVED AUTOCOIDS  |  EICOSANOID BIOSYNTHETIC PATHWAYS", C.purple);

  // Top: membrane → AA flow
  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x:2.8, y:0.65, w:4.4, h:0.72, rectRadius:0.07, fill:{color:C.bgLight}, line:{color:C.white,pt:1.2} });
  s.addText("Membrane Phospholipids", { x:2.8, y:0.65, w:4.4, h:0.38, fontSize:11, bold:true, color:C.white, align:"center", valign:"middle" });
  s.addText("↓ Phospholipase A2 (PLA2)  [Corticosteroids → lipocortin → blocks PLA2]", { x:2.8, y:1.0, w:4.4, h:0.3, fontSize:8.5, color:C.amber, align:"center" });

  s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x:3.7, y:1.45, w:2.6, h:0.62, rectRadius:0.07, fill:{color:C.purple}, line:{color:C.purple,pt:0} });
  s.addText("ARACHIDONIC ACID (AA)", { x:3.7, y:1.45, w:2.6, h:0.62, fontSize:11, bold:true, color:C.white, align:"center", valign:"middle" });

  // Three pathway columns
  const paths = [
    {
      title:"COX PATHWAY",
      sub:"Cyclooxygenase-1 & -2",
      blocked:"NSAIDs / Aspirin block",
      color:C.teal,
      x:0.2,
      lines:[
        "AA → PGG2 → PGH2",
        "(common precursor)",
        "↓ cell-specific synthases",
        "• PGE2 — fever, vasodilation, pain",
        "• PGI2 (Prostacyclin) — ↓platelets, vasodilation",
        "• TxA2 — ↑platelets, vasoconstriction",
        "• PGD2 — bronchoconstriction, sleep",
        "• PGF2α — uterine contraction, ↑IOP",
      ],
    },
    {
      title:"5-LOX PATHWAY",
      sub:"5-Lipoxygenase + FLAP",
      blocked:"Zileuton blocks 5-LOX",
      color:C.orange,
      x:3.45,
      lines:[
        "AA → 5-HPETE → LTA4",
        "(unstable epoxide)",
        "        ↙              ↘",
        "LTA4 hydrolase    LTC4 synthase",
        "      ↓                   ↓",
        "    LTB4          LTC4→LTD4→LTE4",
        "Neutrophil         (cysteinyl-LTs)",
        "chemotaxis      bronchoconstriction",
      ],
    },
    {
      title:"CYP PATHWAY",
      sub:"Cytochrome P450",
      blocked:"(less targeted clinically)",
      color:C.blue,
      x:6.7,
      lines:[
        "AA → EETs",
        "(epoxyeicosatrienoic acids)",
        "→ Vasodilation",
        "→ Renal ion transport",
        "",
        "AA → 20-HETE",
        "→ Vasoconstriction",
        "→ Renal Na⁺ handling",
      ],
    },
  ];
  paths.forEach(p => {
    card(s, p.x, 2.15, 3.1, 3.28, p.color);
    s.addShape(pres.shapes.RECTANGLE, { x:p.x, y:2.15, w:3.1, h:0.36, fill:{color:p.color}, line:{color:p.color,pt:0} });
    s.addText(p.title, { x:p.x+0.08, y:2.15, w:3.0, h:0.36, fontSize:11, bold:true, color:C.bg, valign:"middle", margin:0 });
    s.addText(p.sub, { x:p.x+0.08, y:2.52, w:3.0, h:0.24, fontSize:9, color:p.color });
    s.addText([{text:p.blocked, options:{bold:true, color:C.amber}}], { x:p.x+0.08, y:2.74, w:3.0, h:0.22, fontSize:9 });
    p.lines.forEach((l, li) => {
      s.addText(l, { x:p.x+0.1, y:3.0+li*0.25, w:2.9, h:0.25, fontSize:8.8, color:C.offWhite });
    });
  });

  // Bottom note
  s.addShape(pres.shapes.RECTANGLE, { x:0.2, y:5.38, w:9.6, h:0.2, fill:{color:C.bgMid}, line:{color:C.bgMid,pt:0} });
  s.addText("Corticosteroids block PLA2 via lipocortin → suppress ALL eicosanoid pathways simultaneously (COX + LOX + CYP)", {
    x:0.2, y:5.38, w:9.6, h:0.2, fontSize:8.5, color:C.amber, align:"center",
  });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 8 — PROSTANOIDS IN DETAIL
// ══════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color:C.bg };
  topBar(s, "PART III — PROSTANOIDS (COX Pathway)  |  COX-1 vs COX-2 & Individual Products", C.teal);

  // COX-1 vs COX-2
  hdrCard(s, 0.22, 0.6, 4.7, 0.92, "COX-1 (Constitutive)", C.teal);
  s.addText("Present in virtually all cells; housekeeping roles\n• Gastric mucosal cytoprotection (PGE2/PGI2)\n• Platelet TxA2 synthesis  •  Renal homeostasis\nInhibited by non-selective NSAIDs and aspirin (irreversible)", {
    x:0.35, y:0.95, w:4.45, h:0.54, fontSize:9, color:C.offWhite,
  });

  hdrCard(s, 5.15, 0.6, 4.63, 0.92, "COX-2 (Inducible)", C.orange);
  s.addText("Upregulated by cytokines, shear stress, growth factors\n• Principal source of inflammatory prostanoids\n• Also constitutive in kidney, brain & female reproductive system\nSelectively inhibited by coxibs (celecoxib, etoricoxib)", {
    x:5.28, y:0.95, w:4.4, h:0.54, fontSize:9, color:C.offWhite,
  });

  // Main prostanoid table
  tblHeader(s, 0.22, 1.63, 9.56, ["Prostanoid","Main Source","Receptor / Signal","Key Actions","Clinical Use"], [1.2,1.5,1.6,3.0,2.26], C.teal);

  const pRows = [
    ["PGE2","Many tissues (COX-2)","EP1-EP4\n(Gs, Gi, Gq)","Fever (hypothalamic set-point ↑), vasodilation, pain sensitisation, gastric cytoprotection, uterine contraction","Misoprostol (PGE1): ulcer Rx, cervical ripening, post-partum haemorrhage"],
    ["PGI2\n(Prostacyclin)","Vascular endothelium","IP\nGs → ↑cAMP","Vasodilation, inhibits platelet aggregation, renal vasodilation — opposes TxA2","Epoprostenol, iloprost: pulmonary arterial hypertension"],
    ["TxA2","Platelets (COX-1)","TP\nGq → ↑IP3","Potent vasoconstriction, platelet aggregation (opposes PGI2). t½ <30 sec","Aspirin (irreversible COX-1) → antiplatelet. Coxibs: ↓PGI2 only → ↑CV risk"],
    ["PGD2","Mast cells, brain","DP1, DP2","Vasodilation, bronchoconstriction, eosinophil chemotaxis, sleep regulation","DP2 (CRTH2) antagonists — asthma (investigational)"],
    ["PGF2α","Uterus, lungs","FP\nGq","Uterine contraction (labour), luteolysis, bronchoconstriction, ↑IOP","Latanoprost (PGF2α analog): glaucoma. Dinoprostone: labour induction"],
  ];
  const pBgs = [C.bgLight, C.bgMid, C.bgLight, C.bgMid, C.bgLight];
  pRows.forEach((r, i) => {
    const y = 1.93 + i*0.69;
    tblRow(s, 0.22, y, r, [1.2,1.5,1.6,3.0,2.26], C.teal, pBgs[i]);
    s.addShape(pres.shapes.ROUNDED_RECTANGLE, { x:0.28, y:y+0.13, w:1.08, h:0.42, rectRadius:0.05, fill:{color:C.teal}, line:{color:C.teal,pt:0} });
    s.addText(r[0], { x:0.28, y:y+0.13, w:1.08, h:0.42, fontSize:8.5, bold:true, color:C.bg, align:"center", valign:"middle", margin:0 });
  });

  // COX-2 risk callout
  s.addShape(pres.shapes.RECTANGLE, { x:0.22, y:5.38, w:9.56, h:0.22, fill:{color:C.bgMid}, line:{color:C.red,pt:1} });
  s.addText([
    { text:"COX-2 inhibitors (coxibs): ", options:{bold:true, color:C.red} },
    { text:"suppress PGI2 from endothelium without affecting platelet TxA2 → prothrombotic state → ↑MI/stroke risk (Vioxx withdrawn 2004)", options:{color:C.offWhite} },
  ], { x:0.32, y:5.38, w:9.4, h:0.22, fontSize:8.8, valign:"middle" });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 9 — LEUKOTRIENES, LIPOXINS & PAF
// ══════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color:C.bg };
  topBar(s, "PART III — LEUKOTRIENES  ·  LIPOXINS  ·  PLATELET-ACTIVATING FACTOR (PAF)", C.orange);

  // Leukotriene synthesis pathway
  hdrCard(s, 0.22, 0.62, 5.8, 2.3, "LEUKOTRIENES (5-LOX Pathway)", C.orange);
  s.addText([
    { text:"AA → [5-LOX+FLAP] → 5-HPETE → LTA4 (unstable epoxide)\n", options:{bold:true, color:C.orange} },
    { text:"            ↙  LTA4 hydrolase                 ↘  LTC4 synthase (+glutathione)\n", options:{color:C.gray} },
    { text:"          LTB4                                            LTC4\n", options:{color:C.offWhite} },
    { text:"    (dihydroxy leukotriene)               peptidase → LTD4 → LTE4\n", options:{color:C.lt} },
  ], { x:0.35, y:1.0, w:5.55, h:0.75, fontSize:9.5, fontFace:"Courier New" });

  // LTB4 card
  s.addShape(pres.shapes.RECTANGLE, { x:0.35, y:1.78, w:5.55, h:0.3, fill:{color:C.bgMid}, line:{color:C.bgMid,pt:0} });
  leftBar(s, 0.35, 1.78, 1.1, C.orange);
  pill(s, 0.42, 1.82, 0.65, 0.24, "LTB4", C.orange, C.bg);
  s.addText([
    { text:"Receptor: BLT1/BLT2  |  Source: Neutrophils, macrophages\n", options:{color:C.lt} },
    { text:"Actions: ", options:{bold:true, color:C.orange} },
    { text:"Potent neutrophil chemotaxis & adhesion; amplifies acute inflammation; role in psoriasis, IBD", options:{color:C.offWhite} },
  ], { x:1.12, y:1.78, w:4.7, h:0.55, fontSize:9, valign:"middle" });

  // Cysteinyl-LTs card
  s.addShape(pres.shapes.RECTANGLE, { x:0.35, y:2.03, w:5.55, h:0.32, fill:{color:C.bgLight}, line:{color:C.bgLight,pt:0} });
  leftBar(s, 0.35, 2.03, 0.86, C.red);
  pill(s, 0.42, 2.07, 1.05, 0.24, "LTC4/D4/E4", C.red, C.white);
  s.addText([
    { text:"= SRS-A  |  Source: Mast cells, eosinophils, basophils  |  Receptor: CysLT1, CysLT2\n", options:{color:C.lt} },
    { text:"Actions: ", options:{bold:true, color:C.red} },
    { text:"Bronchoconstriction (1000× > histamine), ↑mucus, ↑vascular permeability → asthma, anaphylaxis", options:{color:C.offWhite} },
  ], { x:1.52, y:2.03, w:4.3, h:0.42, fontSize:9, valign:"middle" });

  // Lipoxins
  s.addShape(pres.shapes.RECTANGLE, { x:0.35, y:2.55, w:5.55, h:0.3, fill:{color:C.bgMid}, line:{color:C.bgMid,pt:0} });
  leftBar(s, 0.35, 2.55, 0.3, C.green);
  pill(s, 0.42, 2.57, 0.9, 0.24, "Lipoxins", C.green, C.bg);
  s.addText([
    { text:"LXA4/LXB4  |  15-LOX + 5-LOX  |  ", options:{color:C.lt} },
    { text:"Anti-inflammatory 'stop signals' — inhibit neutrophil recruitment, promote resolution; aspirin-triggered lipoxins via COX-2", options:{color:C.offWhite} },
  ], { x:1.37, y:2.55, w:4.5, h:0.3, fontSize:9, valign:"middle" });

  // Drug summary
  s.addShape(pres.shapes.RECTANGLE, { x:0.35, y:2.9, w:5.55, h:0.22, fill:{color:C.bgMid}, line:{color:C.amber,pt:1} });
  s.addText([
    { text:"Drugs: ", options:{bold:true, color:C.amber} },
    { text:"Montelukast, zafirlukast (CysLT1 antagonists) — asthma/rhinitis  |  Zileuton (5-LOX inhibitor) — asthma", options:{color:C.offWhite} },
  ], { x:0.48, y:2.9, w:5.35, h:0.22, fontSize:9, valign:"middle" });

  // PAF
  hdrCard(s, 6.25, 0.62, 3.55, 2.85, "PAF (Platelet-Activating Factor)", C.red);
  s.addText([
    { text:"Structure: ", options:{bold:true, color:C.red} },
    { text:"1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine\n(acetylated phospholipid — NOT a classical eicosanoid)\n\n", options:{color:C.offWhite} },
    { text:"Sources: ", options:{bold:true, color:C.red} },
    { text:"Platelets, mast cells, neutrophils,\nmonocytes, vascular endothelium\n\n", options:{color:C.offWhite} },
    { text:"Receptor: ", options:{bold:true, color:C.red} },
    { text:"PAF-R (GPCR — Gi/Gq)\n\n", options:{color:C.offWhite} },
    { text:"Actions:\n", options:{bold:true, color:C.amber} },
    { text:"• Platelet aggregation & activation (femtomolar)\n• Potent bronchoconstriction\n• ↑Vascular permeability\n• Leukocyte activation & chemotaxis\n• Key mediator: anaphylaxis, sepsis, ARDS\n\n", options:{color:C.offWhite} },
    { text:"Metabolism: ", options:{bold:true, color:C.teal} },
    { text:"PAF-acetylhydrolase (PAF-AH) → inactivation\nPAF-AH deficiency → severe asthma in children", options:{color:C.offWhite} },
  ], { x:6.38, y:0.98, w:3.3, h:2.46, fontSize:9.2 });

  // Aspirin-Exacerbated Respiratory Disease box
  s.addShape(pres.shapes.RECTANGLE, { x:0.22, y:3.18, w:9.56, h:0.62, fill:{color:C.bgMid}, line:{color:C.amber,pt:1.2} });
  leftBar(s, 0.22, 3.18, 0.62, C.amber);
  s.addText([
    { text:"Aspirin-Exacerbated Respiratory Disease (Samter's Triad): ", options:{bold:true, color:C.amber} },
    { text:"Aspirin/NSAIDs inhibit COX → AA shunted to 5-LOX → ↑↑cysteinyl leukotrienes → severe bronchoconstriction. ", options:{color:C.offWhite} },
    { text:"Triad: asthma + nasal polyps + aspirin sensitivity. Treatment: leukotriene antagonists + avoid COX inhibitors.", options:{color:C.lt} },
  ], { x:0.38, y:3.18, w:9.3, h:0.62, fontSize:9.5, valign:"middle" });

  // Integration reminder
  s.addShape(pres.shapes.RECTANGLE, { x:0.22, y:3.88, w:9.56, h:1.7, fill:{color:C.bgLight}, line:{color:C.purple,pt:1.2} });
  s.addShape(pres.shapes.RECTANGLE, { x:0.22, y:3.88, w:9.56, h:0.3, fill:{color:C.purple}, line:{color:C.purple,pt:0} });
  s.addText("SYSTEM INTEGRATION — How the three classes interact", { x:0.32, y:3.88, w:9.3, h:0.3, fontSize:10, bold:true, color:C.white, valign:"middle", margin:0 });
  s.addText([
    { text:"Tissue injury/antigen\n", options:{bold:true, color:C.white} },
    { text:"→ Mast cell degranulation: ", options:{bold:true, color:C.amber} },
    { text:"Histamine (amine) + PAF (lipid) → vasodilation, ↑permeability, bronchoconstriction\n", options:{color:C.offWhite} },
    { text:"→ PLA2 activation: ", options:{bold:true, color:C.purple} },
    { text:"AA released → COX → PGE2 (fever/pain), PGI2 (vasodilation), TxA2 (clot); LOX → LTB4 (chemotaxis), LTC4/D4/E4 (bronchoconstriction)\n", options:{color:C.offWhite} },
    { text:"→ Kallikrein activation: ", options:{bold:true, color:C.green} },
    { text:"Bradykinin (peptide) → amplifies vasodilation + pain + stimulates further PG synthesis → ACE (Kininase II) terminates it", options:{color:C.offWhite} },
  ], { x:0.35, y:4.21, w:9.3, h:1.35, fontSize:9.2 });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 10 — MASTER DRUG SUMMARY TABLE
// ══════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color:C.bg };
  topBar(s, "PHARMACOLOGICAL TARGETS — Master Drug Summary: Drugs Acting on Autocoid Pathways", C.teal);

  const drugSections = [
    {
      cat:"H1 Blockers", accent:C.amber,
      rows:[
        ["1st gen","Diphenhydramine, promethazine, chlorpheniramine","Cross BBB → sedation; antimuscarinic; α-blockade","Allergy, motion sickness, anaphylaxis adjunct, acute dystonia"],
        ["2nd gen","Cetirizine, loratadine, fexofenadine","No BBB penetration → no sedation; few autonomic effects","Allergic rhinitis, chronic urticaria — first-line"],
      ],
    },
    {
      cat:"H2 Blockers & 5-HT Drugs", accent:C.orange,
      rows:[
        ["H2 block","Ranitidine, famotidine, cimetidine","Gs→cAMP block on parietal cells → ↓acid","Peptic ulcer disease, GERD, Zollinger-Ellison"],
        ["5-HT drugs","Triptans (sumatriptan): 5-HT1B/D agonist\nSSRIs (fluoxetine): ↑synaptic 5-HT\nOndansetron: 5-HT3 antagonist","Selective receptor subtype activity","Migraine, depression/anxiety, chemo nausea"],
      ],
    },
    {
      cat:"Kinin / Peptide Pathway", accent:C.green,
      rows:[
        ["ACE inhib","Enalapril, lisinopril, ramipril","Block Kininase II → ↑bradykinin; block AT I→II","Hypertension, heart failure, CKD (↑bradykinin = cough!)"],
        ["HAE drugs","Icatibant (B2 block), ecallantide (kallikrein inhib), C1-INH","Target the kinin-generation cascade","Hereditary angioedema — acute & prophylaxis"],
      ],
    },
    {
      cat:"Eicosanoid Pathway", accent:C.purple,
      rows:[
        ["NSAIDs","Ibuprofen, naproxen, diclofenac","Non-selective COX-1+2 inhibition","Anti-inflammatory, analgesic, antipyretic"],
        ["Aspirin","Low dose: 75–300 mg","Irreversible COX-1 acetylation → ↓TxA2 (platelets)","Antiplatelet — ACS, stroke prevention"],
        ["Coxibs","Celecoxib, etoricoxib","Selective COX-2 → ↓PGI2 only","Arthritis — note ↑CV risk (↓PGI2/↑TxA2 imbalance)"],
        ["LT drugs","Montelukast (CysLT1)\nZileuton (5-LOX)","Block leukotriene pathway","Asthma, allergic rhinitis, aspirin-exacerbated RD"],
        ["PG analogs","Misoprostol (PGE1): gastric/cervical\nLatanoprost (PGF2α): IOP\nEpoprostenol (PGI2): PAH","Selective receptor agonism","Ulcer prophylaxis, glaucoma, PAH"],
        ["Steroids","Dexamethasone, prednisolone","↑Lipocortin → ↓PLA2 → block ALL eicosanoids","Anti-inflammatory, anaphylaxis, immunosuppression"],
      ],
    },
  ];

  let currentY = 0.6;
  drugSections.forEach((sec) => {
    s.addShape(pres.shapes.RECTANGLE, { x:0.22, y:currentY, w:9.56, h:0.28, fill:{color:sec.accent}, line:{color:sec.accent,pt:0} });
    s.addText(sec.cat, { x:0.3, y:currentY, w:9.4, h:0.28, fontSize:9.5, bold:true, color:C.bg, valign:"middle", margin:0 });
    currentY += 0.28;
    const bgs = [C.bgLight, C.bgMid];
    sec.rows.forEach((r, ri) => {
      const rh = r[0]==="5-HT drugs" ? 0.58 : (r[0]==="LT drugs"||r[0]==="PG analogs"?"0.44":0.36);
      const hh = parseFloat(rh);
      tblRow(s, 0.22, currentY, r, [1.05, 3.1, 2.9, 2.51], sec.accent, bgs[ri%2]);
      currentY += hh;
    });
    currentY += 0.05;
  });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 11 — SUMMARY TABLE
// ══════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color:C.bg };
  topBar(s, "SUMMARY TABLE — Autocoids at a Glance", C.teal);

  const thead = [[
    { text:"CLASS",    options:{ bold:true, color:C.bg, fill:{color:C.teal} } },
    { text:"AUTOCOID", options:{ bold:true, color:C.bg, fill:{color:C.teal} } },
    { text:"PRECURSOR / SYNTHESIS", options:{ bold:true, color:C.bg, fill:{color:C.teal} } },
    { text:"RECEPTOR / SIGNAL",     options:{ bold:true, color:C.bg, fill:{color:C.teal} } },
    { text:"KEY ACTIONS",           options:{ bold:true, color:C.bg, fill:{color:C.teal} } },
  ]];

  function row(cls, name, pre, rec, act, bg) {
    return [
      { text:cls,  options:{ bold:true, color:C.amber, fill:{color:bg} } },
      { text:name, options:{ color:C.offWhite, fill:{color:bg} } },
      { text:pre,  options:{ color:C.lt, fill:{color:bg} } },
      { text:rec,  options:{ color:C.teal, fill:{color:bg} } },
      { text:act,  options:{ color:C.offWhite, fill:{color:bg} } },
    ];
  }
  const trows = [
    row("AMINE","Histamine","L-Histidine → histidine decarboxylase","H1(Gq) H2(Gs) H3(Gi) H4(Gi)","Allergy, inflammation, gastric acid secretion, itch, bronchoconstriction",C.bgLight),
    row("","Serotonin (5-HT)","L-Tryptophan → tryptophan hydroxylase → AADC","5-HT1(Gi) 5-HT2(Gq) 5-HT3(ion ch.) 5-HT4(Gs)","GI motility, platelet aggregation, mood/anxiety, vasoconstriction, emesis",C.bgMid),
    row("PEPTIDE","Bradykinin","Kininogens + kallikreins; degraded by ACE (Kininase II)","B1(inducible) B2(constitutive) — Gq","Vasodilation (NO+PGI2), pain, ↑vascular permeability, bronchoconstriction",C.bgLight),
    row("","ANP / BNP","Cardiac atria/ventricles; proteolytic cleavage of preproANP","GC-A receptor → ↑cGMP","Natriuresis, diuresis, vasodilation, ↓RAAS (renin, aldosterone, AVP)",C.bgMid),
    row("","Endothelins","Preproendothelin → ECE → ET-1","ETA(Gq vasoconstriction) ETB(vasodilation)","ET-1 = most potent endogenous vasoconstrictor; PAH target (bosentan)",C.bgLight),
    row("","Substance P","Gene-encoded; tachykinin family (11 aa)","NK1 receptor — Gq","Pain transmission, neurogenic inflammation, vasodilation, emesis",C.bgMid),
    row("LIPID","PGE2 / PGI2 / TxA2","Arachidonic acid via COX-1/COX-2","EP, IP, TP receptors","Fever, pain, hemostasis, gastric protection, reproduction, vasoregulation",C.bgLight),
    row("","LTC4 / D4 / E4","Arachidonic acid via 5-LOX","CysLT1, CysLT2","Bronchoconstriction (SRS-A), ↑mucus, ↑vascular permeability — asthma",C.bgMid),
    row("","LTB4","Arachidonic acid via 5-LOX","BLT1, BLT2","Potent neutrophil chemotaxis; acute inflammation amplification",C.bgLight),
    row("","PAF","Membrane phospholipids via PLA2+acetyltransferase","PAF-R (GPCR — Gi/Gq)","Platelet activation, bronchoconstriction, anaphylaxis, sepsis",C.bgMid),
  ];

  s.addTable([...thead, ...trows], {
    x:0.22, y:0.62, w:9.56,
    colW:[0.85, 1.45, 2.2, 2.3, 2.76],
    fontSize:8.5, margin:3, rowH:0.48,
    border:{ pt:0.5, color:"1A3354" },
  });

  s.addText("Katzung's Basic & Clinical Pharmacology 16e  ·  Goodman & Gilman's 13e  ·  Ganong's Review of Medical Physiology 26e", {
    x:0, y:5.38, w:10, h:0.22, fontSize:7.5, color:C.gray, align:"center",
  });
}

// ── WRITE FILE ────────────────────────────────────────────────
pres.writeFile({ fileName: "/home/daytona/workspace/autocoids-pptx/Autocoids_Pharmacological_Basis.pptx" })
  .then(() => console.log("✅  File saved successfully"))
  .catch(e => { console.error("ERROR:", e.message); process.exit(1); });